Data on a doctoral project being supervised by MMEC’s Jeni Harden, one of the authors of this paper, show children with epilepsy often have limited knowledge about epilepsy. Publicly readily available information about epilepsy, aside from written information, specifically designed with children with mind are sparse. The current study shows that an animated film on early medical abortion might be valuable in providing information for women considering this procedure. Extrapolating from this, an animation film about epilepsy could be helpful in providing children with much needed information about the disease.

Linking routinely collected social work, education and health data to enable monitoring of the health and health care of school-aged children in state care ('looked after children') in Scotland: a national demonstration project.

Dr Wood and colleagues demonstrate the strong potential of linking Scotland’s routine administrative social, education and health data to investigate the health outcomes of school aged children. By extending their method they propose to be able to include information on children who are not in public funded schooling.

Seizures, syndromes, and etiologies in childhood epilepsy: The International League Against Epilepsy 1981, 1989, and 2017 classifications used in a population-based cohort.

In one of the first published studies to use the new ILAE classification scheme for epilepsy, and apply it to the largest validated and phenotyped epilepsy cohorts identified from a birth cohort worldwide, the Norway-UK researchers show: (1) the new classification allows for a greater precision in diagnoses which may help with prognosis, treatment and trying to find causes but as this requires detailed investigative results, may result in more epilepsies being unclassifiable pending results/availability of tests. (2) Despite advances in technology, the cause of epilepsy still remains unknown in most children.

MMEC Pre-clinical lead Mike Cousin and his team reveal a form of severe intellectual disability and epilepsy found in a single patient was caused by a mutation in the SYP gene. They went on to show that this mutation specifically affected movement of a key protein for neuron communication – synaptobrevin II. They showed that this defect was also seen with other human mutations in SYP, this time from X-linked intellectual disability. Therefore correcting the altered movement of synaptobrevin II may be a potential avenue for therapeutic intervention in both epilepsy and intellectual disability.

InvestigatingSexBias in the AQ-10: A ReplicationStudy.

Autism is a common comorbidity in epilepsy and those on the milder end of the spectrum can be difficult to identify. Thus, screening methods for autism are important. This study confirms that a novel screening instrument (AQ-10) which determines who would benefit from more detailed testing, is not biased against females. Nonetheless the authors suggest one item to be replaced.

Fragile X syndrome (FXS) is the most common form of inherited X-linked intellectual disability, with patients often displaying epilepsy. FXS is thought to be caused by excessive synthesis of specific types of proteins controlled by FMRP, which is mutated in FXS. . The Osterweil group showed common FXS symptoms (including seizures) can be reversed in a model system by activating a pathway dependent on the neurotransmitter acetylcholine. Interestingly proteins for this pathway are increased in FXS, showing that enhancement of specific proteins may be beneficial preventing FXS symptoms, including seizures.

Chris Derry from MMEC and colleagues discover mutations in COL18A1 gene in four sisters. These sisters display Lennox-Gastaut type severe refractory epilepsy and abnormality in the formation of the front of the brain. This finding is novel since it identifies a genetic, inherited cause for Lennox Gastatut Syndrome. Previously this genetic mutation was usually found in another neurological disorder therefore this study expands the types of diseases/conditions that occur due to abnormalities in COL18A1.

Estimatingnumbers of children with cerebralpalsy: a call to action.

Authors

Wood R. Dev Med Child Neurol. 2017 Aug; 59(8).

Description

Dr. Wood comments on an original article by Glinianaia et al. on “Predicting the prevalence of cerebral palsy by severity level in children aged 3 to 15 years across England and Wales by 2020” Dr. Wood emphasises that the key message arising from the paper by Glinianaia et al. is that, austerity and service cuts notwithstanding, the need for robust, integrated services for children (and their families) with complex needs is unlikely to diminish in the short to medium term. Regardless of advances in prevention, there will always be children with significant impairment and disability, and how we collectively organize and deliver services to meet their needs will remain a measure of our society.

Susan Duncan, head of the adult epilepsy service in Edinburgh, and other members of the UK wide epilepsy mortality group put forward suggestions to optimise pregnancy care in women with epilepsy. The aim is to reduce maternal mortality and morbidity in children exposed to anti-epileptic medication whilst they are in the womb.

The APGAR Score, usually given at 1 minute, 5 minutes, and 10 minutes after birth is often used to predict mortality within the first month of life. Furthermore lower scores are associated with long term health problems in children who survive past the first month of life. Dr. Wood and colleagues show that there is a large variation in APGAR scoring amongst countries, likely due to national scoring practices, makes the APGAR score an unsuitable indicator for comparing health in the newborn across countries.

Incidence and Prevalence of Childhood Epilepsy: A Nationwide Cohort Study.

In the second of a series of papers from a collaboration between the Norwegian Institute of Public Health and the University of Edinburgh, the researchers provide up to date information on the incidence of childhood epilepsy. The importance, strength and merits of analysing data collected routinely in clinical practice, often referred to as “Big Data” is increasingly being recognised. This paper demonstrates the importance of the validation of epilepsy diagnoses in such data, since a third of children can be erroneously coded as having epilepsy when they do not. The now validated epilepsy cohort is part of a much larger birth cohort and will allow the researchers to examine the development of children with epilepsy compared to those without, the prenatal and postnatal factors that lead to an increased risk for epilepsy and related neurodevelopmental problems, and factors that improve outcomes.

Febrile seizures occur in 3 per 100 children between the ages of 6 months to 5 years. They generally last less than 5 minutes but can go on for longer than 30 minutes. These longer seizures, prolonged febrile seizures, are thought to cause brain damage. In this study of a unique group of children with prolonged febrile seizures, researchers from UCL and the University of Edinburgh report findings that suggest prolonged febrile seizures can interfere with usual development of how different parts of the brain connect with each other but adopts to this within 8 years through changes in the microstructure and organisation of the connective tracts of the brain.

Reduced local input to fast-spiking interneurons in the somatosensory cortex in the GABAA γ2 R43Q mouse model of absence epilepsy.

Developmental concerns and or problems can exist prior to the onset of seizures. Why cognitive and behavioural problems occur in a high proportion of people with epilepsy is unclear. This study shows that in an experimental model of a specific type of epilepsy, childhood absence epilepsy, there are changes in the way that the brain is usually connected PRIOR to the onset of seizures.

A (free) radical approach reveals the physiological function of different synaptic vesicle pools.

Authors

Cousin MA. J Physiol. 2017 Feb 15;595(4):1005-1006.

Description

Synaptic vesicles (SVs) store neurotransmitter inside brain cells and during neuronal activity are triggered to release their contents to evoke neuronal communication. This short commentary article highlighted our growing understanding that not all SVs are created equal, and that there are different populations that mediate different types of neurotransmission. This may be important for neurotransmitter release during epilepsy, and identifying which SVs are responsible may allow excessive neurotransmission to be limited.

Alterations in the properties of neonatal thalamocortical synapses with time in in vitro slices.

Authors

Luz LL, Currie SP, Daw MI. PLoS One. 2017 Feb 8;12(2):e0171897.

Description

Preclinical, non-human studies are important to increase understanding of and development of treatments for epilepsy. Brain cells are constantly being formed and lost in the living brain with those that remain forming connections between them. This study shows the way that brain cells communicate with each other in experimental studies of brain slices in specialised preparations changes over time. Thus, in experiments using this technique, this has to be borne in mind.

The complex hierarchical topology of EEG functional connectivity.

Authors

Smith K, Escudero J. J Neurosci Methods. 2017 Jan 30;276:1-12.

Description

EEGs have traditionally been used to help in the diagnosis and treatment of epilepsy. There is increasing interest in using EEG to develop networks to enhance our understanding of how the brain is connected and how it works. This paper provides insight into the complex ways that brain networks are organised.

Grid cells' need for speed.

Authors

Gonzalez-Sulser A, Nolan MF. Nat Neurosci. 2016 Dec 27;20(1):1-2.

Description

Grid-firing fields of neurons in the entorhinal cortex are thought to require inputs encoding running speed. Glutamatergic projections from the medial septum may be one of the inputs that provide these speed signals.

This study showed that in Scotland, children with cancer are at no higher risk of having low Vitamin D levels compared to children in the general Scottish population. However, in both groups, low levels are common. Older children with cancer, or those who are overweight or not taking vitamin D supplements are more likely to have low levels. The study collaborators in oncology, gastroenterology and neurology services at the Royal Hospital for Sick Children in Edinburgh recommended that supplementation and monitoring should implemented. Vitamin D levels in the “healthy” control group of children were obtained through a parallel study funded by the Roald Dahl Marvellous Children’s Charity, examining Vitamin D levels in Scottish children with epilepsy versus those without.

The brain electrical activity varies throughout the day and even at the same time period, there can be marked variation of electrical activity within different parts of the brain. These electrical activities have a rhythm and are described as oscillations. Maintenance of these oscillations are linked to learning and if they become abnormal could be associated with development of seizures. In this paper, the authors report on how the medial septum of the brain (a potential target for novel epilepsy treatments) influences oscillations.

Quantifying and exploring camouflaging in men and women with autism.

The co-occurrence of epilepsy and autism is common. From a study carried out by a consortium of researchers, Dr. Auyeung and colleagues investigated if and how people with autism “camouflage” their social communication difficulties. They found that the degree of camouflaging was not significantly influenced by age or IQ. On average, women with autism had higher camouflaging scores than men with autism with substantial variability in both groups. Greater camouflaging was associated with more depressive symptoms in men.

There are more than 40 different types of epilepsy, and there are many autism spectrum conditions (ASC). This study addresses the possibility of misdiagnosis or underdiagnosis using the AQ-10, a screening test for ASC recommended by the National Institute of Clinical Excellence. Dr. Auyeung and colleagues show that some items were biased towards males and others to females but overall there was no bias. This supports the continued use of AQ-10 as a screening test, but caution should be exercised when interpreting responses to individual items.

There is increasing evidence of the role of genetic abnormalities in diseases of the nervous system, including epilepsy. Identification of a genetic abnormality is insufficient on its own and more work is needed to understand the changes in function that result from this event and thus the changes in biology in humans. Understanding this can be highly beneficial with prognostication and development of therapies. In this paper, Prof Abbott and colleagues show how a novel technique CRISPR/Cas 9 can be used to introduce genetic abnormalities in human brain cells. This is usually a very difficult process for brain cells that are grown in dishes. This new work opens up potential to study the mechanism of human brain diseases including Rett Syndrome and EEF1A2 disorder.

Seizures arise because of an imbalance between excitatory and inhibitory mechanisms in the brain. In this paper, the authors discuss evidence for continuous attractor network models that account for grid firing by synaptic interactions between excitatory and inhibitory cells.

The detection of spikes on EEGs is an important part of the diagnosis and treatment of epilepsy. Seizure detection devices rely on automated detection of such spikes but if there are irregularities in the trace from movement or other artefacts, this can be difficult or impossible. The authors report their discovery of a novel method of detecting spikes and announce the free availability of the code.